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Flashcards in HIV Deck (41):
1

What would happen to the virus if tat was inhibited?

It would be unable to transcribe structural proteins

2

What is the function of the LTR's in viral RNA?

They serve as RNA pol II promoters once the viral nucleic acid is integrated into host DNA

3

What has been associated with mutated nef?

Patients don't develop full-blown AIDS

4

I'm doing these quickly...

Sorry if they suck.

5

What is targeted by drugs in order to prevent the "absolutely obligatory" step in viral replication?

Reverse transcriptase

6

What is a provirus?

Virus that has integrated it's DNA intermediate to the host DNA

*resembles a normal gene

7

Name a cell (reservoir) in which HIV virus can integrate and "hide out" for decades.

Resting T cells

8

Enzyme necessary for virus integration

Integrase

9

What is notable about HIVs requirements for integration into the host DNA?

Cell does not need to be actively dividing (can be a terminally differentiated cell)

10

Describe the early phase of HIV gene expression (3)

1. No transcription of the integrated provirus
2. Occurs during long, latency periods
3. Expresses low levels of proteins necessary for virus to persist

11

Describe the late phase of HIV gene expression

1. Structural proteins synthesized (high levels)
2. tat turns weak promoter into strong promoter (binds TAR)
3. rev allows transport of unspliced mRNAs from nucleus (usually have to be spliced to leave nucleus)

12

Where does HIV assembly occur?

Host plasma mem

13

What is necessary for HIV budding?

Host cell's ubiquitin ligases

14

What enzyme is responsible for "maturation" cleavage of core proteins? What would happen if it was inhibited?

viral protease

inhibition = release of a non-infectious virus

15

What is generated by the dimerization of gag-pol?

active protease

16

Family and subfamily of HIV

Retroviridae
Lentivirus

17

Which is more pathogenic: HIV1 or HIV2?

HIV1

18

What are 2 ways in which HIV1 is subdivided, based on distribution?

1. M (major) vs O (outlier)
2. "clades" or genetic subtypes (determined by gag/envelope sequences)

(for example HIV1-M, Clade B)

19

What are 2 ways in which HIV1 is subdivided, based on cellular features?

1. Chemokine co-receptor utilization
CXCR4 + CCR5
2. Syncytium-inducing capability

20

CXCR4 is __-tropic, while CCR5 is __-tropic

CXCR4 (T-tropic); CCR5 (M-tropic)

*M = on macrophages
*T = on Tcells (and other cells)

21

How many copies of RNA are in the inner HIV capsid?

2 (survival advantage; RNA mutates a lot)

22

Name 3 proteins (+function) that are involved in the HIV envelope.

p24 = capsid protein (forms cylindrical core of envelope)
gp120 = receptor binding
gp41 = membrane fusion activity

23

3 enzymes that are common drug targets:

reverse transcriptase
protease
integrase
(these are all required for replication; they are originally one protein that is cleaved)

24

Accessory protein that transports mRNA

rev

25

What structures are involved in virus entry and replication?

1. CD4 and gp120 bind (gp120 undergoes a conf change to bring the cells closer)
2. gp120 binds to a chemokine receptor (CCR5, CXCR4, etc)
3. Eventually gp41 is activated, resulting in fusion

26

RNA is converted into a _____, _sDNA molecule.

linear, double (this has to happen)

27

(Review slide) Summary of Key Points:

1. Infections are characterized by lifelong persistence (can integrate and evade)
2. High mutation rate (changes in tropism; undergoes selection)
3. Variation is disease presentation (inf, development of cancers, wasting, etc)
4. Variation in time to disease onset
5. Stages: Acute, Latent (asymptomatic), Symptomatic (AIDS)

28

3 Routes of Transmission

1. Direct sexual contact (50%M, 50%F)
2. Blood and blood products (mostly IV drug users these days)
3. Perinatal transmission (more HIV+ mothers taking AZT has improved the rates)

29

Fluids that contain viruses (top 3):

Semen
Cervical secretions
Breast milk
(less in Urine, Saliva, Tears, Cerebrospinal fluid--mostly because it needs to be in cells)

30

What are the 3 stages of infection? (brief description included)

1. acute: flu-like symptoms occur ~3-6wks while the virus infects T cells and macrophages (big immune response)

2. asymptomatic: virus is latent, but stil replicating at high levels--CD4 cell #'s rebound

3. symptomatic: occurs when CD4 count drops dramatically, immune dysfunction = patient susceptible to opportunistic infections + AIDS-related cancers

31

2 criteria used for predicting disease progression:
*high yield

1. CD4+ T cell count (lower = faster progression)
2. viral load (high = faster AIDS onset)

*note: prior to drop in CD4, pts lose CD8 due to CD4-related immune dysfunction (less prolif of Tcells and IL2)

32

3 determinants of HIV resistance:

1. Specific MHC-I allele
5-10% do not progress to clinical disease

2. CCR5 mutation (del = premature stop)
homozygous = "resistant"
heteozygous = slower disease progression

3. Nef-deletion mutation

33

Once symptomatic HIV infection is diagnosed, survival is ~___ years

2

34

WHat mutation increases HIV susceptibility?

loss of a cell-surface protein; same mutation makes Africans resistant to malaria

35

6 Dx Tests:

(this is probably not very high yield, according to objectives)

1. Dipstick: saliva, blood, serum
2. ELISA: assay for p24
3. Western: confirms ELISA
= antibody tests
4. PCR: detects viral DNA
5. RT-PCR: quantifies viral RNA in plasma
6. branched DNA: detects viral RNA and DNA
= nucleic acid tests to determine the amount of virus

36

What drug disrupts DNA chain elongation synthesis?

nuc analog reverse transcriptase inhibitors (bind to RT)

37

WHat drug binds adjacent to the nucTP pocket and inhibits synthesis of provirus DNA?

Non-nucleoside reverse transcriptase inhibitors

38

What drugs bind to active site on the protease and prevents gag-pol cleavage?

Protease Inhibitors

39

What drugs bind to gp41 and prevents membrane fusion?

Entry Inhibitors
(one new drug is a CCR5 antagonist)

40

What drugs inhibit strand transfer of viral DNA to host cell DNA?

Integrase Inhibitor (final step in integration)

41

T/F: A resistance mutant can arise in a week.

T (give a cocktail of drugs; if you have to change them, don't just change 1--change all and don't "just add" a drug)